We have described a specific, sensitive radioimmunoassay (RIA) for myelin basic protein (Cohen et al., J. Neurochem. 25: 371, l975). This assay has been applied to cerebrospinal fluid (CSF) of multiple sclerosis patients. The myelin basic protein is present in multiple sclerosis patients with acute exacerbation, and during the demyelinative attack, high levels of myelin basic protein are found (10-50 ng/ml). Myelin basic protein is absent from the cerebrospinal fluid of patients with nondemyelinative neurologic disease and multiple sclerosis patients in remission. Thus, radioimmunoassay of myelin basic protein in cerebrospinal fluid is a useful test for active demyelination (Cohen et al., New Engl. J. Med. 295: l455, l976). These findings will be extended to identify the exact properties of the basic protein in spinal fluid (i.e., whether it is membrane-bound, present as peptide fragments, associated with lipids or other proteins, etc.). Immunochemical and molecular filtration methods will be used. In addition, we will determine if these properties change during a demyelinative attack. Optic neuritis patients will be followed for several years to determine if their initial CSF basic protein (30% of optic neuritis patients looked at to date have CSF basic protein) correlates with the outcome of their illness. These studies will provide basic information relating to human demyelination. Myelination will be investigated using immunochemical probes such as RIA, immunoprecipitation and immunoperoxidase localization to study basic protein synthesis and myelin formation in normal and mutant mouse brain. Questions such as the cellular sites and mechanism of myelin synthesis in normal and pathological brain will be addressed.